1. Field of the Invention
The present invention provides and includes monoclonal antibodies (MoAbs or mAbs) specific or preferentially selective for a PCBP-1 antigen, hybridoma lines that secrete these PCBP-1 antibodies or antibody fragments, and the use of such antibodies and antibody fragments to detect PCBP-1 antigens, particularly those expressed by cancer cells. The present invention also includes antibodies that are specific for or show preferential binding to a soluble form of PCBP-1 (sPCBP-1). The present invention further includes chimeric and humanized antibodies, processes for producing monoclonal, chimeric, and humanized antibodies using recombinant DNA technology, and therapeutic uses of these antibodies, particularly in the treatment of cancer. The present invention further includes methods and kits for the immunodetection and immunotherapy of cells for samples which express a PCBP-1 antigen of the present invention.
2. Background
One human carcinoma tumor antigen is PCBP-1 (poly(rC) binding protein-1). Pcbp-1 is an intronless human gene reported to have been generated by retrotransposition of a fully processed PCBP-2 mRNA. It is also reported to be located on chromosome 2 (70.17-70.17 Mb). The protein encoded by the Pcbp-1 gene is a reported multifunctional protein. PCBP-1, along with PCBP-2 and hnRNPK, are reported to form the major cellular poly(rC)-binding proteins. Pcbp-1 has been sequenced. See UniProt Q15365, Q53SS8, Q14975; OMIM 601209; NCBI Gene 5093; NCBI RefSeq NP_006187; NCBI RefSeq NM_006196, NP_006187; NCBI UniGene 5093; and NCBI Accession AK130439, AAA91317. Homologues of Pcbp-1 are also reported, including, but not limited to, homologues of Pcbp-1 in the mouse (see NCBI UniGene 23983; UniProt P60335; and NCBI RefSeq NM_011865, NP_035995), dog, and rat.
PCBP-1 has also been reported to regulate transcription for a few individual promoters, to be important for the metabolism and gene expression of HIV-1 and poliovirus, and to stimulate IRES-mediated translation initiation in vitro and in vivo (Mitchell et al., 2003). It has also been reported to be modestly increased in the epidermis of elderly individuals (Gromov et al., Mol Cell Proteomics 2(2):70-84, 2003).
The breast cancer-specific survival rates of women with one or two positive nodes were found to have similar likelihoods of long-term survival; however, women with three positive nodes experienced significantly reduced survival compared to those with one or two involved nodes. (Tai, P., et al., Prognostic Significance of Number of Positive Nodes: A Long-Term Study of One to Two Nodes Versus Three Nodes in Breast Cancer Patients, International Journal of Radiation Oncology; 77 (1) p. 180-187 (May 2010)). Accordingly, there is a need for an additional molecular marker, more than just lymph node status, of overall survival, particularly for women with three or more positive nodes. There is also a need for a molecular marker to determine metastatic status of a ductal breast cancer in women with any lymph node involvement.